The present invention relates to the use of human neutrophil lipocalin (HNL) as a diagnostic marker, in particular for diagnosis in connection with inflammation that may have a bacterial origin. The determination of the HNL level in a sample from a patient assists in discriminating between bacterial and viral infection.
The main function of human neutrophils is to sense, approach, and destroy invading micro-organisms, in particular pyogenic bacteria. Invading micro-organisms cause degranulation and exocytosis of various granule proteins from neutrophils (Henson, J. Immunol. 107 (1971) 1535-46). The determination of the granule proteins released from neutrophils has long been used as indicators of neutrophil activation in infections and inflammation (Schmekel et al., Inflam. 14 (1990) 447-54; and Lash et al., Blood 61(1983) 885-8). C-reactive protein (CRP) is an acute phase reactant produced in the liver and its measurement has been used in the early diagnosis of bacterial infections.
The results presented herein indicate a sequence identity between HNL and human neutrophil 24 kD N-formyl-peptide binding protein, 25 kD .alpha.-2-microglobulin-related protein (Triebel et al., FEBS Lett. 314 (1992) 386-) and neutrophil gelatinase-associated lipocalin (NGAL) (Kjeldsen et al., J. Biol. Chem. 268 (1993) 10425-). The preliminary isolation of HNL has been published (Venge et al., J. Leukocyte Biol. Supplement 1 (1990) 28). During the priority year the complete purification/characterization and assay of human neutrophil lipocalin have been published (Xu et al., Scand. J. Lab. Invest. 54 (1994) 365-76 and Xu et al., J. Immunol. Meth. 171 (1994) 245-52).